The Host Defense Group of the Laboratory of Respiratory Biology, Division of Intramural Research, National Institute of Environmental Health Sciences, headed by Michael B. Fessler, MD now enters its third year at the NIEHS since inception. We have increased our staffing to 6 active laboratory members. Accomplishments include an original publication (Smoak K et al., Journal of Immunology 2008;180(5):3305-12) that defines a novel role for the nuclear receptor Liver X Receptor in modulation of pulmonary innate immunity, 3 review articles published or in press, a published and Pubmed-indexed meeting abstract on Liver X Receptor in lung inflammation (Madenspacher JH et al., Proc Am Thorac Soc. 2008 Apr;5(3):366), and an original manuscript on proteomic analysis of macrophage rafts that has been resubmitted with minor revisions (Molecular & Cellular Proteomics). Additional accomplishments include a 2009 FARE abstract award for Research Fellow Suraj Dhungana, organization and chairing by Dr. Fessler of an NIEHS Symposium on Lipid Raft Biology, hosting by Dr. Fessler of the NIEHS Distinguished Lecturer for May 2008 (Kai Simons), appointing of Dr. Fessler to the American Thoracic Society (ATS) RCMB Assembly, delivery of 5 regional research seminars by Dr. Fessler, chairing by Dr. Fessler of a genomics/proteomics poster session at the 2008 ATS International Conference, and presentation by Dr. Fessler of a poster at the Gordon Research Conference on Lipoprotein Metabolism. In addition, substantial data has been collected on 5 active research projects in the laboratory: 1) characterization of apoplipoprotein A-I as a novel stimulus of innate immunity; 2) characterization of viral fusion proteins as novel innate immune stimuli; 3) proteomic discovery of novel signaling proteins recruited to macrophage lipid rafts in response to LPS; 4) identification of a modulatory role of dyslipidemia upon pulmonary innate immunity in a murine model of inhaled LPS and in human asthma; and 5) investigation of a role for cholesterol trafficking regulators in pulmonary innate immune responses. Presently, 2 new original manuscripts are under final preparation and will be submitted imminently.